The major objective of our studies is to characterize cell surface structures on T and B lymphocytes as well as on non-T accessory cells (AC) which, in addition to the specific antigen receptor, are involved in the process of lymphocyte activation. Over the past 5 years we have developed a number of monoclonal antibodies (mAbs) to mouse T lymphocyte cell surface antigens which are capable of stimulating or inhibiting T cell triggering. We have defined the Thy-1 antigen as one of the critical signal transducing molecules in lymphoid cells. A large panel of mAbs to Thy-1 were capable of inducing T cell activation. Furthermore, following transfection of Thy-1 into several murine B lymphomas, crosslinking of Thy-1 resulted in an elevation of cytoplasmic free calcium (Ca2+i), one of the initial critical events in lymphocyte activation. Studies have also implicated a distinct group of cell surface alloantigens, the products of the Ly-6 locus, as important molecules involve in the physiological activation of T cells. Lastly, we have combined studies with mAbs to cell surface antigens with molecular studies of T cell receptor gene expression to characterize a unique population of T cells, the Thy-1+ dendritic cells, which populate murine epidermis. The ultimate goals of our studies are to fully understand the regulatory mechanisms that control T cell activation and differentiation. mAbs to lymphocyte surface antigens should prove to be useful tools in these studies and may also prove to be attractive candidates for in vivo therapeutic use in attempts to modulate or abrogate an ongoing immune response.